Pulmonary involvement in Fabry disease: effect of plasma globotriaosylsphingosine and time to initiation of enzyme replacement therapy. Issue 1 (21st April 2018)

• Record Type: Journal Article
• Authors: Franzen, Daniel; Haile, Sarah R; Kasper, David C; Mechtler, Thomas P; Flammer, Andreas J; Krayenbühl, Pierre A; Nowak, Albina
• Is Part Of: BMJ open respiratory research. Volume 5:Issue 1(2018)
• Publication Date: 2018-04-21
• Subjects: rare lung diseases -- copd ÀÜ mechanisms -- systemic disease and lungs; Respiratory organs -- Diseases -- Periodicals; Respiratory organs -- Diseases -- Treatment -- Periodicals; Respiratory therapy -- Periodicals; 616.2005
• DOI: 10.1136/bmjresp-2018-000277
• Languages: English
• ISSNs: 2052-4439

Abstract

Abstract : Introduction: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by mutations of GLA gene leading to reduced α-galactosidase activity and resulting in a progressive accumulation of globotriaosylceramide (Gb3) and its deacylated derivative, globotriaosyl-sphingosine (Lyso-Gb3). Plasma Lyso-Gb3 levels serve as a disease severity and treatment monitoring marker during enzyme replacement therapy (ERT). Methods: Adult patients with AFD who had yearly pulmonary function tests between 1999 and 2015 were eligible for this observational study. Primary outcome measures were the change in z-score of forced expiratory volume in the first second (FEV1 ) and FEV1 /FVC over time. Plasma Lyso-Gb3 levels and the age of ERT initiation were investigated for their association with lung function decline. Results: Fifty-three patients (42% male, median (range) age at diagnosis of AFD 34 (6–61) years in men, 34 (13–67) in women) were included. The greatest decrease of FEV1 /FVC z-scores was observed in Classic men (−0.048 per year, 95% CI −0.081 to –0.014), compared with the Later-Onset men (+0.013, 95% CI −0.055 to 0.082), Classic women (−0.008, 95% CI −0.035 to +0.020) and Later-Onset women (−0.013, 95% CI −0.084 to +0.058). Cigarette smoking (P=0.022) and late ERT initiation (P=0.041) were independently associated with faster FEV1 decline. FEV1 /FVC z-score decrease was significantly reduced after initiation of ERT initiation (−0.045 compared with −0.015, P=0.014). Furthermore, there was a trend towards a relevant influence of Lyso-Gb3 (P=0.098) on airflow limitation with age. Conclusion: Early ERT initiation seems to preserve pulmonary function. Plasma Lyso-Gb3 is maybe a useful predictor for airflow limitation. Classic men need a closer monitoring of the lung function.